PROJECT SUMMARY Social determinants of health (SDoH)?the conditions in which people are born, grow, work, live, and age?are key drivers of health and health disparities. Children with medical complexity are particularly at-risk given their high healthcare need and utilization. Although the American Academy of Pediatrics and payers such as the Centers for Medicaid and Medicare Services are now recommending medical providers screen for SDoH at visits, studies have not yet demonstrated the impact of SDoH screening and referral interventions on improving child health and have fallen short of exploring potential mechanisms by which such interventions could improve health outcomes. Children with sickle cell anemia (SCA) are an ideal population in which to study the impact of SDoH interventions given the high prevalence of poverty and unmet material needs among this population and the disease?s significant morbidity and mortality. This proposal addresses a timely clinically- and policy-relevant research gap by: (1) implementing a SDoH intervention in two outpatient pediatric hematology clinics and gathering preliminary data to assess its impact on child health; and (2) characterizing the potential mechanisms by which addressing SDoH may lead to improved health outcomes. Our team has developed, tested, and implemented a SDOH intervention (WE CARE) which relies on existing clinical processes to screen for unmet material needs and refer parents to community services; efficacy data demonstrates its positive impact on parental receipt of community resources. We now propose conducting a pragmatic pilot cluster RCT to examine the implementation of WE CARE as standard of care in two of the four hematology clinics. To preliminarily examine outcomes, we will recruit and follow 100 parents of children with SCA (25 per site) for one year in order to explore how addressing unmet social needs within the delivery of medical care may improve healthcare utilization and health outcomes. Given the limitations of applying existing theoretical frameworks to culturally diverse populations such as those with SCA, we will also employ a mixed methods approach to characterizing how SDoH influences disease management processes. Our specific aims are to: (1) Implement WE CARE in two pediatric hematology clinics in order to field test key study logistics and understand the facilitators and barriers to implementation and accelerate its adoption; (2) Obtain population- specific empirical estimates of study parameters to plan a large-scale multi-site cluster RCT of WE CARE that will definitely assess its impact on improving health outcomes for children with SCA; and (3) Qualitatively assess possible mechanisms linking SDoH interventions to improved health outcomes. This proposal is innovative because it challenges the current clinical practice and research paradigms for children with SCA. It has significant implications for child health policy and is a critical step in potentially transforming the delivery of healthcare for medically complex children.